Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation
Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation
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碳水化合物反应元件结合蛋白（ChREBP）与结肠癌进展相关并有助于细胞增殖
DOI：
10.1038/s41598-020-60903-9
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发表时间：
2020-03-06
影响因子：
4.6
通讯作者：
Gu, Jiang
中科院分区：
文献类型：
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作者：
Lei, Yu;Zhou, Shuling;Gu, Jiang
癌症的特征在于重新编程的葡萄糖代谢，以促进细胞生长和增殖。碳水化合物反应元件结合蛋白（ChREBP）是一种葡萄糖介导的转录因子，强烈调节糖酵解和脂肪生成途径。它已被证明与代谢疾病有关，如肥胖症，糖尿病和非酒精性脂肪肝疾病。然而，它与癌症的关系还没有得到很好的理解。在这项研究中，ChREBP的表达进行了评估，在结肠组织阵列包含正常结肠组织和癌组织在不同的临床阶段。还在结肠癌患者队列中测量了ChREBP的组织mRNA水平。我们发现ChREBP mRNA和蛋白表达在结肠癌组织中与健康结肠相比显著增加（p < 0.001），并且它们的表达与结肠恶性肿瘤正相关（对于mRNA，p = 0.002;对于蛋白，p < 0.001）。结肠癌中的脂肪生成基因（ChREBP VL 6和SCD 1）的表达也与结肠恶性程度呈正相关（对于两个基因，p < 0.001）。在体外，用siRNA转染ChREBP抑制结肠癌细胞系（HT 29、DLD 1和SW 480）的细胞增殖并诱导细胞周期停滞，而不改变细胞凋亡。糖酵解和脂肪生成途径被抑制，但p53途径被激活后ChREBP敲低。综上所述，ChREBP表达与结肠恶性肿瘤相关，并且其可能通过促进合成代谢途径和抑制p53来促进细胞增殖。此外，ChREBP可能是一种新的临床有用的生物标志物，以评估结肠癌的恶性程度。
Cancers are characterized by reprogrammed glucose metabolisms to fuel cell growth and proliferation. Carbohydrate response element binding protein (ChREBP) is a glucose-mediated transcription factor that strongly regulates glycolytic and lipogenic pathways. It has been shown to associate with metabolic diseases, such as obesity, diabetes and non-alcoholic fatty liver diseases. However, how it associates with cancers has not been well understood. In this study, ChREBP expression was assessed by immunohistochemistry in colon tissue arrays containing normal colon tissue and cancer tissue at different clinical stages. Tissue mRNA levels of ChREBP were also measured in a cohort of colon cancer patients. We found that ChREBP mRNA and protein expression were significantly increased in colon cancer tissue compared to healthy colon (p < 0.001), and their expression was positively correlated to colon malignancy (for mRNA, p = 0.002; for protein p < 0.001). Expression of lipogenic genes (ELOVL6andSCD1) in colon cancer was also positively associated with colon malignancy (for both genes, p < 0.001).In vitro, ChREBP knockdown with siRNA transfection inhibited cell proliferation and induced cell cycle arrest without changes in apoptosis in colon cancer cell lines (HT29, DLD1 and SW480). Glycolytic and lipogenic pathways were inhibited but the p53 pathway was activated after ChREBP knockdown. Taken together, ChREBP expression is associated with colon malignancy and it might contribute to cell proliferation via promoting anabolic pathways and inhibiting p53. In addition, ChREBP might represent a novel clinical useful biomarker to evaluate the malignancy of colon cancer.